DEVELOPABLE INTERVENTIONAL GUIDEWIRE FOR HYPERPOLARIZED 129XE MAGNETIC RESONANCE IMAGING AND PREPARATION METHOD THEREOF

Abstract

The present invention relates to the technical field of medical devices, and in particular, to a developable interventional guidewire for hyperpolarized .sup.129Xe MRI and a preparation method thereof. The interventional guidewire includes a guidewire body, a cladding layer wrapped around a surface of the guidewire body, a Zn(II)-PDA modified layer adhered to a surface of the cladding layer, and a developing film layer coated on the Zn(II)-PDA modified layer. The Zn(II)-PDA modified layer is introduced on the guidewire body and, through activation treatment with 2-methylimidazole and solvothermal synthesis, a continuous and dense ZIF-8 film layer is prepared as the developing film layer for the hyperpolarized .sup.129Xe MRI.

Claims

1. An application of a ZIF-8 film in development of an interventional guidewire for hyperpolarized .sup.129Xe magnetic resonance imaging (MRI), wherein the interventional guidewire is composed of a guidewire body, a cladding layer wrapped around a surface of the guidewire body, a Zn(II)-PDA modified layer adhered to a surface of the cladding layer, and a ZIF-8 developing film layer coated on the Zn(II)-PDA modified layer; the guidewire body is a core wire with magnetic compatibility; the ZIF-8 developing film layer is a continuous and dense ZIF-8 film; and ZIF-8 in the ZIF-8 film captures .sup.129Xe inhaled into a human body and generates a nuclear magnetic resonance signal of .sup.129Xe@ZIF-8 to enable the development of the interventional guidewire under the hyperpolarized .sup.129Xe MRI through computer data processing and image reconstruction.

2. An interventional guidewire with a ZIF-8 developing film capable of development under hyperpolarized .sup.129Xe MRI, wherein the interventional guidewire is composed of a guidewire body, a cladding layer wrapped around a surface of the guidewire body, a Zn(II)-PDA modified layer adhered to a surface of the cladding layer, and the ZIF-8 developing film layer coated on the Zn(II)-PDA modified layer; the guidewire body is a core wire with magnetic compatibility; and the ZIF-8 developing film layer is a continuous and dense ZIF-8 film used to capture .sup.129Xe gas molecules and generate a nuclear magnetic resonance signal of .sup.129Xe@ZIF-8 to enable the development of the interventional guidewire under the hyperpolarized .sup.129Xe MRI through computer data processing and image reconstruction.

3. The interventional guidewire of claim 2, wherein the guidewire body is made of nickel-aluminum alloy, metallic titanium, ceramics, plastics, or composite materials; and the cladding layer is a layer of high molecular weight polymer such as polytetrafluoroethylene, polyurethane, nylon, polylactic acid, or polyether ether ketone.

4. A preparation method of the interventional guidewire of claim 2, comprising the following steps: (1) preparation of a Zn(II)-PDA modified layer: wrapping a cladding layer around a surface of a guidewire body to obtain a to-be-treated interventional guidewire; pre-adding ZnCl.sub.2 into a dopamine-containing tris(hydroxymethyl)aminomethane hydrochloride buffer solution to obtain a zinc-doped dopamine coating solution; and immersing the clean to-be-treated interventional guidewire in the zinc-doped dopamine coating solution, stirring at room temperature for complete reaction, and performing washing and drying to obtain the interventional guidewire with the Zn(II)-PDA modified layer, wherein the cladding layer is a layer of high molecular weight polymer, and the guidewire body is a core wire with magnetic compatibility; (2) activation of the Zn(II)-PDA modified layer: immersing the interventional guidewire with the Zn(II)-PDA modified layer obtained in the step (1) in a methanol solution of 2-methylimidazole; and allowing for activation at 25-65 C. for more than 2 hours to obtain an activated interventional guidewire; and (3) preparation of a ZIF-8 developing film layer: putting the activated interventional guidewire obtained in the step (2) into a hydrothermal autoclave; using 2-methylimidazole, zinc nitrate hexahydrate, and anhydrous methanol as raw materials to prepare a ZIF-8 synthetic solution; transferring the ZIF-8 synthetic solution to the hydrothermal autoclave and allowing for reaction at 65-120 C. for more than 24 hours; and after the reaction is completed, allowing for cooling to room temperature and performing washing and drying overnight to obtain the developable interventional guidewire for hyperpolarized .sup.129Xe MRI.

5. The preparation method of claim 4, wherein the dopamine-containing tris (hydroxymethyl) aminomethane hydrochloride buffer solution is prepared by dissolving dopamine hydrochloride in a tris (hydroxymethyl) aminomethane hydrochloride buffer solution with a pH of 8.55 and a concentration of 10 mM.

6. The preparation method of claim 5, wherein a mass ratio of the ZnCl.sub.2 to the dopamine hydrochloride added in the step (1) is 2:1.

7. The preparation method of claim 4, wherein a concentration of the methanol solution of 2-methylimidazole in the step (2) is 1.5 M, and a molar ratio of the 2-methylimidazole to the zinc nitrate hexahydrate in the step (3) is 2:1.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0029] FIG. 1 shows a schematic structural diagram of an interventional guidewire with a ZIF-8 developing film layer prepared in a step (3) in an Embodiment 1 of the present invention;

[0030] FIG. 2 shows a schematic cross-sectional diagram of an interventional guidewire with a ZIF-8 developing film layer prepared in the step (3) in the Embodiment 1 of the present invention;

[0031] FIG. 3A shows a scanning electron micrograph of a ZIF-8 developing film layer on an interventional guidewire prepared in the step (3) in the Embodiment 1 of the present invention;

[0032] FIG. 3B shows a scanning electron micrograph of a ZIF-8 developing film layer on an interventional guidewire without a Zn(II)-PDA modified layer and without activation prepared in the Embodiment 1 of the present invention;

[0033] FIG. 3C shows a scanning electron micrograph of a ZIF-8 developing film layer on an interventional guidewire with a Zn(II)-PDA modified layer and without activation prepared in the Embodiment 1 of the present invention;

[0034] FIG. 4 shows a scanning electron micrograph of an interventional guidewire coated with a ZIF-8 developing film layer prepared in the step (3) in the Embodiment 1 of the present invention;

[0035] FIG. 5 shows attenuated total reflection infrared absorption spectra of a polytetrafluoroethylene cladding layer on an interventional guidewire prepared in a step (1), a Zn(II)-PDA modified layer prepared in a step (2), and a ZIF-8 developing film layer prepared in the step (3) in the Embodiment 1 of the present invention; FIG. 6 shows a .sup.129Xe spectrum of an interventional guidewire with a developing

[0036] film layer for hyperpolarized .sup.129Xe MRI prepared in an Embodiment 2, obtained from direct gaseous sampling;

[0037] FIG. 7 shows a .sup.129Xe spectrum of an interventional guidewire with a developing film layer for hyperpolarized .sup.129Xe MRI prepared in an Embodiment 3, obtained in an aqueous solution; and

[0038] FIG. 8 shows a .sup.129Xe spectrum of an interventional guidewire with a developing film layer for hyperpolarized .sup.129Xe MRI in an Embodiment 4, obtained in fetal bovine serum.

[0039] Reference signs in the accompanying drawings: [0040] 1. guidewire body; 2. polytetrafluoroethylene cladding layer; 3. Zn(II)-PDA modified layer; and 4. ZIF-8 developing film layer.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0041] The present invention will be further illustrated below in detail in conjunction with embodiments. It should be understood that these embodiments are only intended to illustrate the present invention rather than to limit the claimed scope of the present invention. It should also be understood that after reading the content of the present invention, those skilled in the art may make various modifications to the present invention, and these equivalent forms shall also fall within the scope defined by the appended claims of the present invention.

[0042] The technical solution of the present invention will be described in detail in conjunction with embodiments and with reference to FIGS. 1-8.

[0043] The sources of the main reagents and materials used in the following Embodiments 1-4 are as follows: [0044] sodium hydroxide, zinc chloride, dopamine hydrochloride, zinc nitrate hexahydrate, 2-methylimidazole, and anhydrous methanol were purchased from Sinopharm, and tris (hydroxymethyl) aminomethane hydrochloride was purchased from Shanghai Aladdin, all of analytical grade.

[0045] Fetal bovine serum was of special grade produced in South America (HYCEZMBIO).

[0046] Unless otherwise specified, the aforementioned reagents were used directly without further purification. All water used was deionized.

[0047] In order to verify the feasibility of the method of the present invention, the following Embodiment 1 used a fiberglass reinforced plastic rod with an inner diameter of 0.80 mm as a guidewire body and a polytetrafluoroethylene heat-shrink tube as a cladding layer wrapped around the surface of the fiberglass reinforced plastic rod to prepare a to-be-treated interventional guidewire.

[0048] The operation of wrapping the heat-shrink tube around the fiberglass reinforced plastic rod was carried out as follows: [0049] slip the heat-shrink tube (HST-PTFE (1.7:1) type Teflon heat-shrink tube from Shenzhen Hongjiexin Technology Co., Ltd., with an inner diameter of 1.0-1.2 mm before heat shrinkage) on the fiberglass reinforced plastic rod with an inner diameter of 0.80 mm, use a hot air gun to retract the Teflon heat-shrink tube at a high temperature of 350 C., and then tightly wrap the tube around the outer surface of the fiberglass reinforced plastic rod. After heat shrinkage, the wall thickness of the heat-shrink tube became 0.140.03 mm.

Embodiment 1

[0050] A preparation method of a developable interventional guidewire for hyperpolarized .sup.129Xe MRI, including the following steps: [0051] (1) preparation of a Zn(II)-PDA modified layer: weigh 0.1592 g of tris (hydroxymethyl) aminomethane hydrochloride and add it into 100 mL of deionized water, and then stir the solution until complete dissolution; add 28 mg of sodium hydroxide powder to adjust the pH of the solution to obtain a tris (hydroxymethyl) aminomethane hydrochloride buffer solution with a concentration of 10 mM; add 0.2 g of dopamine hydrochloride to the tris (hydroxymethyl) aminomethane hydrochloride buffer solution, stir the solution until dissolution, and then add 0.4 g of zinc chloride to obtain a zinc-doped dopamine coating solution; cut the to-be-treated interventional guidewire into segments of 7 cm long, clean the segments ultrasonically with ethanol and deionized water for 15 minutes, immerse the cleaned interventional guidewire in the aforementioned zinc-doped dopamine coating solution, and then stir the solution and allow for reaction for 24 hours at room temperature in the presence of oxygen and away from light, with a rotation speed of 200 r/min; and after the reaction is completed, wash the interventional guidewire several times with deionized water and dry it in an oven at 65 C. for 12 hours to obtain an interventional guidewire with a Zn(II)-PDA modified layer; [0052] (2) activation of the Zn(II)-PDA modified layer: weigh 1.2565 g of 2-methylimidazole powder and dissolve it in 10 mL of anhydrous methanol to obtain a methanol solution of 2-methylimidazole; immerse the interventional guidewire with the Zn(II)-PDA modified layer obtained in the step (1) in the methanol solution of 2-methylimidazole, and heat the solution for activation reaction in an oil bath at 50 C. for 3 hours; and then take out the interventional guidewire and wash away residual 2-methylimidazole with anhydrous methanol to obtain an activated interventional guidewire with the Zn(II)-PDA modified layer; [0053] (3) preparation of a ZIF-8 developing film layer: put the activated interventional guidewire with the Zn(II)-PDA modified layer obtained in the step (2) into a 100 mL hydrothermal autoclave; add 2.36 g of zinc nitrate hexahydrate into a 250 ml conical flask, and then add 50 mL of anhydrous methanol into the flask; add 1.32 g of 2-methylimidazole into another 250 ml conical flask, and then add 50 mL of anhydrous methanol into the flask; sonicate the solutions in the two conical flasks until they are clear and transparent to obtain a 2-methylimidazole solution and a zinc nitrate solution respectively; add the 2-methylimidazole solution into the zinc nitrate solution while stirring, and wait until they are evenly mixed to obtain a ZIF-8 synthetic solution; transfer the ZIF-8 synthetic solution to the aforementioned autoclave, seal and place it in an electric blast drying oven at 85 C. for reaction for 24 hours, and after the reaction is completed, cool it to room temperature; and finally, take out the interventional guidewire, wash it several times with anhydrous methanol, and then dry it at 60 C. overnight to obtain an interventional guidewire with a ZIF-8 developing film layer on the surface thereof, that is, an interventional guidewire with a developing film layer for hyperpolarized .sup.129Xe MRI; [0054] (4) replacement of the aforementioned interventional guidewire activated with the Zn(II)-PDA modified layer in the step (3) with a to-be-treated interventional guidewire having gone through ultrasonic cleaning for 15 minutes to prepare an interventional guidewire without a Zn(II)-PDA modified layer and without activation; and [0055] (5) replacement of the aforementioned interventional guidewire activated with the Zn(II)-PDA modified layer in the step (3) with the interventional guidewire with the Zn(II)-PDA modified layer and without activation prepared in the step (1).

[0056] FIGS. 1 and 2 show a schematic structural diagram and cross-sectional diagram of the interventional guidewire with the ZIF-8 developing film layer prepared in the step (3) in the Embodiment 1 of the present invention. The interventional guidewire had an inner diameter of 0.80 mm and included: a guidewire body 1, a polytetrafluoroethylene cladding layer 2, a Zn(II)-PDA modified layer 3, and a ZIF-8 developing film layer 4, where the developing film layer 4 was composed of ZIF-8 nanoparticles; the polytetrafluoroethylene cladding layer 2 was wrapped around the outer surface of the guidewire body 1; the Zn(II)-PDA modified layer 3 was coated on the surface of the polytetrafluoroethylene cladding layer 2; and the ZIF-8 developing film layer 4 was connected to the polytetrafluoroethylene cladding layer 2 via the Zn(II)-PDA modified layer 3 as an intermediate layer.

[0057] FIG. 3A shows a scanning electron micrograph of the ZIF-8 developing film layer 4 on the interventional guidewire prepared in the step (3) in this embodiment, from which it can be seen that ZIF-8 particles accumulate on the interventional guidewire to form a continuous and dense ZIF-8 film layer; FIG. 3B shows a scanning electron micrograph of the ZIF-8 developing film layer on the interventional guidewire without the Zn(II)-PDA modified layer and without activation prepared in this embodiment; and FIG. 3C shows a scanning electron micrograph of the ZIF-8 developing film layer on the interventional guidewire with the Zn(II)-PDA modified layer and without activation prepared in this embodiment. It can be seen form FIGS. 3b and 3c that only loosely accumulated ZIF-8 particles appear on the interventional guidewire, and no dense ZIF-8 film layer is formed. The experimental results of scanning electron microscopy shown in FIGS. 3a, 3b, and 3c prove that the lack of Zn(II)-PDA modified layer or the Zn(II)-PDA modified layer without activation cannot ensure the successful preparation of the ZIF-8 developing film layer on the surface of the guidewire, and the preparation and activation of the Zn(II)-PDA modified layer are the key to preparing a continuous and dense ZIF-8 developing film layer on the interventional guidewire.

[0058] FIG. 4 shows a scanning electron micrograph of the interventional guidewire coated with the ZIF-8 developing film layer prepared in the step (3) in the Embodiment 1 of the present invention; and FIG. 5 shows attenuated total reflection infrared absorption spectra of the polytetrafluoroethylene cladding layer 2 on the interventional guidewire prepared in the step (1), the Zn(II)-PDA modified layer 3 prepared in the step (2), and the ZIF-8 developing film layer 4 prepared in the step (3) in the Embodiment 1 of the present invention. It can be seen from the figures that in addition to the infrared absorption peak of polytetrafluoroethylene, the characteristic absorption peaks of Zn(II)-PDA also appear near 1496 cm.sup.1, 1607 cm.sup.1, and 3421 cm.sup.1 in the infrared absorption spectrum of the Zn(II)-PDA modified layer on the interventional guidewire, which shows that the Zn(II)-PDA modified layer is successfully modified on the cladding layer of the interventional guidewire. In the infrared absorption spectrum of the ZIF-8 developing film layer on the interventional guidewire, the sharp peaks at 693 cm.sup.1, 758 cm.sup.1, 953 cm.sup.1, 1180 cm.sup.1, and 1310 cm.sup.1 all belong to bending vibration peaks of the imidazole ring; the peaks at 1424 cm.sup.1 and 1457 cm.sup.1 are both stretching vibration peaks of the imidazole ring; the peaks at 994 cm.sup.1 and 1146 cm.sup.1 are characteristic stretching vibration peaks of CN in imidazole; and the peak at 1578 cm.sup.1 is a characteristic stretching vibration peak of CN in imidazole. These absorption peaks indicate that the ZIF-8 film layer is successfully modified on the polytetrafluoroethylene cladding layer of the interventional guidewire via the Zn(II)-PDA modified layer as a connecting layer.

[0059] The above results all indicate successful preparation of the ZIF-8 developing film layer.

Embodiment 2

[0060] A .sup.129Xe spectrum test of the interventional guidewire with the developing film layer for hyperpolarized .sup.129Xe MRI prepared in the Embodiment 1, obtained from direct gaseous sampling, which was carried out as follows: [0061] perform a .sup.129Xe NMR experiment with a 400 MHz (9.4 T) Bruker AV400 wide-aperture spectrometer (Bruker Biospin, Ettlingen, Germany) equipped with a microimaging gradient coil, with an RF pulse frequency of the Xe core being 110.7 MHz; use a 10 mm dual resonance probe (.sup.129Xe and 1H, PABBO 400W1/S2 BB-HD-10Z) having a rectangular pulse with a flip angle of 90 for generating a .sup.129Xe NMR spectrum; generate a hyperpolarized .sup.129Xe gas by spin exchange optical pumping using a continuous flow polarization device, with a degree of nuclear spin polarization being approximately 20%; inject a mixed gas consisting of 10% N.sub.2, 88% He and 2% Xe by volume (Xe may be 86% enriched .sup.129Xe or naturally abundant .sup.129Xe, with the latter used in this embodiment) directly into a 10 mm nuclear magnetic tube for 20 seconds, and then wait for 3 seconds before signal acquisition; set the sample temperature to 300 K on the NMR spectrometer; and [0062] put the interventional guidewire of 7 cm long with the developing film layer for hyperpolarized .sup.129Xe MRI prepared in the step (3) in the Embodiment 1 into the nuclear magnetic tube for gas contact and directly perform the aforementioned .sup.129Xe NMR experiment.

[0063] The results of the .sup.129Xe spectrum of the interventional guidewire obtained through direct gaseous sampling in this embodiment are shown in FIG. 6. Two signals appeared in the .sup.129Xe spectrum: one was attributed to gaseous .sup.129Xe, with the chemical shift =0 ppm, and the other at 85 ppm was what the applicant wanted to obtain, i.e. the NMR signal of .sup.129Xe@ZIF-8 generated by the ZIF-8 developing film layer capturing .sup.129Xe molecules in the mixed gas. The above results indicate that the interventional guidewire modified with the developing film layer for hyperpolarized .sup.129Xe MRI can obtain the NMR signal of .sup.129Xe@ZIF-8 under gaseous conditions.

Embodiment 3

[0064] A .sup.129Xe spectrum test of the interventional guidewire with the developing film layer for hyperpolarized .sup.129Xe MRI prepared in the Embodiment 1, obtained in an aqueous solution, which was carried out as follows: [0065] perform a .sup.129Xe NMR experiment with a 400 MHz (9.4 T) Bruker AV400 wide-aperture spectrometer (Bruker Biospin, Ettlingen, Germany) equipped with a microimaging gradient coil, with an RF pulse frequency of the Xe core being 110.7 MHz; use a 10 mm dual resonance probe (.sup.129Xe and 1H, PABBO 400W1/S2 BB-HD-10Z) having a rectangular pulse with a flip angle of 90 for generating a .sup.129Xe NMR spectrum; generate a hyperpolarized .sup.129Xe gas by spin exchange optical pumping using a continuous flow polarization device, with a degree of nuclear spin polarization being approximately 20%; inject a mixed gas consisting of 10% N.sub.2, 88% He and 2% Xe by volume (Xe may be 86% enriched .sup.129Xe or naturally abundant .sup.129Xe, with the latter used in this embodiment) directly into a 10 mm nuclear magnetic tube for 20 seconds, and then wait for 3 seconds to ensure that any bubbles generated are completely collapsed before signal acquisition; set the sample temperature to 300 K on the NMR spectrometer; and [0066] put the interventional guidewire of 7 cm long with the developing film layer for hyperpolarized .sup.129Xe MRI prepared in the step (3) in the Embodiment 1 into the nuclear magnetic tube, add 3 mL of deionized water, and perform the aforementioned .sup.129Xe NMR experiment.

[0067] The results of the .sup.129Xe spectrum of the interventional guidewire in the aqueous solution in this embodiment are shown in FIG. 7. Two signals appeared in the .sup.129Xe spectrum: one was attributed to dissolved .sup.129Xe, with the chemical shift =193.5 ppm, and the other at 85 ppm was what the applicant wanted to obtain, i.e. the NMR signal of .sup.129Xe@ZIF-8 generated by the ZIF-8 developing film layer capturing .sup.129Xe molecules in the aqueous solution. The above results indicate that the interventional guidewire modified with the developing film layer for hyperpolarized .sup.129Xe MRI can obtain the NMR signal of .sup.129Xe@ZIF-8 in the aqueous solution.

Embodiment 4

[0068] A .sup.129Xe spectrum test of the interventional guidewire with the developing film layer for hyperpolarized .sup.129Xe MRI prepared in the Embodiment 1, obtained in fetal bovine serum, which was carried out as follows: [0069] perform a .sup.129Xe NMR experiment with a 400 MHz (9.4 T) Bruker AV400 wide-aperture spectrometer (Bruker Biospin, Ettlingen, Germany) equipped with a microimaging gradient coil, with an RF pulse frequency of the Xe core being 110.7 MHz; use a 10 mm dual resonance probe (.sup.129Xe and 1H, PABBO 400W1/S2 BB-HD-10Z) having a rectangular pulse with a flip angle of 90 for generating a .sup.129Xe NMR spectrum; generate a hyperpolarized .sup.129Xe gas by spin exchange optical pumping using a continuous flow polarization device, with a degree of nuclear spin polarization being approximately 20%; inject a mixed gas consisting of 10% N.sub.2, 88% He and 2% Xe by volume (Xe may be 86% enriched .sup.129Xe or naturally abundant .sup.129Xe, with the latter used in this embodiment) directly into a 10 mm nuclear magnetic tube for 20 seconds, and then wait for 3 seconds to ensure that any bubbles generated are completely collapsed before signal acquisition; set the sample temperature to 300 K on the NMR spectrometer; and [0070] put the interventional guidewire of 7 cm long with the developing film layer for hyperpolarized .sup.129Xe MRI prepared in the step (3) in the Embodiment 1 into the nuclear magnetic tube, add 0.6 mL of fetal calf serum and 2.4 mL of deionized water, and perform the aforementioned .sup.129Xe NMR experiment.

[0071] The results of the .sup.129Xe spectrum of the interventional guidewire in the fetal bovine serum in this embodiment are shown in FIG. 8. Three signals appeared in the .sup.129Xe spectrum: one was attributed to dissolved .sup.129Xe, with the chemical shift =194.3 ppm, one at 82.6 ppm was what the applicant wanted to obtain, i.e. the NMR signal of .sup.129Xe@ZIF-8 generated by the ZIF-8 developing film layer capturing .sup.129Xe molecules in the fetal bovine serum, and the last one at 2.9 ppm was caused by a few of bubbles produced by gas injection into the nuclear magnetic tube. The above results indicate that the interventional guidewire modified with the developing film layer for hyperpolarized .sup.129Xe MRI can obtain the NMR signal of .sup.129Xe@ZIF-8 in complex biological systems and has a high sensitivity to .sup.129Xe.

[0072] The above provides a detailed description of the exemplary embodiments of the present invention. It should be understood that those skilled in the art can make many modifications and changes according to the concept of the present invention without creative efforts. Therefore, any technical solution that can be obtained by those skilled in the art according to the concept of the present invention through logical analysis, logical inference, or limited experiments on the basis of the prior art shall fall within the scope of protection determined by the claims.